Concerted Activity of Tyrosine Phosphatase SHP-2 and Focal Adhesion Kinase in Regulation of Cell Motility

• DOI: 10.1128/mcb.19.4.3125
• Publication Date: 2015-10-26T10:18:19Z
• Authors: Santos Mañes; Emilia Mira; Concepción Gómez-...; Zhizuang Joe Zhao; Rosa Ana Lacalle; Carlos Martínez-A.
• Keywords: Paxillin; PTK2

The coordinated interplay of substrate adhesion and deadhesion is necessary for cell motility. Using MCF-7 cells, we found that insulin-like growth factor I (IGF-I) induces the to vitronectin collagen in a dose- time-dependent manner, suggesting IGF-I triggers activation different integrins. On other hand, promotes association insulin receptor 1 with focal kinase (FAK), paxillin, tyrosine phosphatase SHP-2, resulting FAK paxillin dephosphorylation. Abrogation SHP-2 catalytic activity dominant-negative mutant (SHP2-C>S) abolishes IGF-I-induced dephosphorylation, cells expressing SHP2-C>S show reduced IGF-I-stimulated chemotaxis compared either mock- or wild-type-transfected cells. This impairment migration recovered by reintroduction catalytically active SHP-2. Interestingly, SHP-2-C>S larger number contacts than wild-type participates integrin deactivation process. Although regulates mitogen-activated protein activity, inhibitor PD-98059 has only marginal effect on migration. role as general regulator induced chemotactic agents integrins discussed.